Engineering the human pluripotent stem cell microenvironment to direct cell fate

Abstract

Human pluripotent stem cells (hPSCs), including both embryonic stem cells and induced pluripotent stem cells, offer a potential cell source for research, drug screening, and regenerative medicine applications due to their unique ability to self-renew or differentiate to any somatic cell type. Before the full potential of hPSCs can be realized, robust protocols must be developed to direct their fate. Cell fate decisions are based on components of the surrounding microenvironment, including soluble factors, substrate or extracellular matrix, cell-cell interactions, mechanical forces, and 2D or 3D architecture. Depending on their spatio-temporal context, these components can signal hPSCs to either self-renew or differentiate to cell types of the ectoderm, mesoderm, or endoderm. Researchers working at the interface of engineering and biology have identified various factors which can affect hPSC fate, often based on lessons from embryonic development, and they have utilized this information to design in vitro niches which can reproducibly direct hPSC fate. This review highlights culture systems that have been engineered to promote self-renewal or differentiation of hPSCs, with a focus on studies that have elucidated the contributions of specific microenvironmental cues in the context of those culture systems. We propose the use of microsystems technologies for high-throughput screening of spatial-temporal presentation of cues, as this has been demonstrated to be a powerful approach for differentiating hPSCs to desired cell types.

Microenvironmental Regulation of Telomerase Isoforms in Human Embryonic Stem Cells

“…The interactions between hESCs and their surrounding microenvironment are critical for the regulation of inter-and intracellular processes, where subtle changes in this niche can induce dramatic alterations in hESC phenotype [64]. Herein, we have shown that a low (2%)-O 2 atmosphere induced nuclear localization of elevated TERT levels that correlated with hESC proliferation/cell survival in the undifferentiated state, without significantly increasing telomerase activity levels.…”

Improved efficiency of definitive endoderm induction from human induced pluripotent stem cells in feeder and serum-free culture system

“…expressing pancreatic cells. In such a complex step-wise method, efficiency of the target cell production is always a major issue (Hazeltine et al 2013), and pushing the majority of cells into pancreatic differentiation requires every induction step in the process to be highly efficient, including that of definitive endoderm. Many methods to induce definitive endoderm cells from embryonic stem cells (ESCs)/iPSCs have been reported with similar results.…”

“…In particular, the establishment of human-induced pluripotent stem cells (hiPSCs) (Takahashi and Yamanaka 2006;Takahashi et al 2007) potentially makes it possible to induce appropriate tissues and organs from cells of patients themselves (Drews et al 2012). Pluripotent stem cells (PSCs) have now been made experimentally into almost every cell type by controlling step-wise differentiation with cytokines and by manipulating every microenvironmental condition (Hazeltine et al 2013). However, several obstacles hamper researchers from fully realizing the medical potential of hiPSCs, with the major ones being low induction efficiency and contamination of animal-derived substances.…”

Designing biomaterials for tissue engineering based on the deconstruction of the native cellular environment

“…Fig. 1B present some of such important features, recognised by many authors [18,19], and how they could be reproduced in biomaterials and culturing conditions. The deconstruction of these essential biophysical and structural elements can be reproduced synthetically by the correct design of biomaterialsbased scaffolds that could be then used as frameworks for simplified in vitro niches.…”